Cargando…

Complete Depletion of Daratumumab Interference in Serum Samples from Plasma Cell Myeloma Patients Improves the Detection of Endogenous M-Proteins in a Preliminary Study

Background: Therapeutic humanized IgG1 kappa monoclonal antibody (t-mAb), daratumumab (DARA) is a Food and Drug Administration approved drug for the treatment of relapsed/refractory plasma cell myeloma (PCM). DARA appears on serum protein electrophoresis (SPEP) and on serum immunofixation (sIFE) as...

Descripción completa

Detalles Bibliográficos
Autores principales: Vakili, Hana, Koorse Germans, Sharon, Dong, Xiuhua, Kansagra, Ankit, Patel, Hetalkumari, Muthukumar, Alagarraju, Hashim, Ibrahim A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235820/
https://www.ncbi.nlm.nih.gov/pubmed/32295157
http://dx.doi.org/10.3390/diagnostics10040219
_version_ 1783536043286331392
author Vakili, Hana
Koorse Germans, Sharon
Dong, Xiuhua
Kansagra, Ankit
Patel, Hetalkumari
Muthukumar, Alagarraju
Hashim, Ibrahim A.
author_facet Vakili, Hana
Koorse Germans, Sharon
Dong, Xiuhua
Kansagra, Ankit
Patel, Hetalkumari
Muthukumar, Alagarraju
Hashim, Ibrahim A.
author_sort Vakili, Hana
collection PubMed
description Background: Therapeutic humanized IgG1 kappa monoclonal antibody (t-mAb), daratumumab (DARA) is a Food and Drug Administration approved drug for the treatment of relapsed/refractory plasma cell myeloma (PCM). DARA appears on serum protein electrophoresis (SPEP) and on serum immunofixation (sIFE) as an IgG kappa monoclonal immunoglobulin protein (M-protein), complicating the assessment of the patients’ response to therapy. A more ominous threat to patient safety can occur with the misinterpretation of the presence of a small t-mAb spike as being the residual product of the patient’s neoplastic clone, presented either as oligoclonality or new clonality, which could result in incorrect interpretation of failure to achieve remission. Methods: In this report, we describe a novel and cost-effective technique based on biotinylated recombinant CD38 and streptavidin-coated magnetic beads to capture and remove residual DARA present in PCM patient serum samples. The treated samples are then run like regular samples on SPEP and sIFE. We validated this simple technique in DARA-spiked PCM samples and patient samples on DARA treatment. Results: Our simple capture technique completely extracted DARA in all of the tested serum specimens and allowed the assessment of residual M-protein without DARA interference. The results were reproducible and highly specific for DARA, and did not have any impact on endogenous M-protein migration and quantification by SPEP and sIFE. The cost of this technique is much lower and it can be performed in-house with a very short turnaround time compared to the currently available alternative methods. There is a great need for such reflex technologies to avoid interpretation errors. Conclusions: This method is an effective way to eliminate DARA interference in SPEP and sIFE, and can be easily implemented in any clinical laboratory without any patent restriction. This simple technique can be adopted for other t-mAbs using their respective ligands and will help to reduce additional doses of toxic treatment and further testing in patients on t-mAbs with a false positive M-protein spike.
format Online
Article
Text
id pubmed-7235820
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72358202020-05-22 Complete Depletion of Daratumumab Interference in Serum Samples from Plasma Cell Myeloma Patients Improves the Detection of Endogenous M-Proteins in a Preliminary Study Vakili, Hana Koorse Germans, Sharon Dong, Xiuhua Kansagra, Ankit Patel, Hetalkumari Muthukumar, Alagarraju Hashim, Ibrahim A. Diagnostics (Basel) Article Background: Therapeutic humanized IgG1 kappa monoclonal antibody (t-mAb), daratumumab (DARA) is a Food and Drug Administration approved drug for the treatment of relapsed/refractory plasma cell myeloma (PCM). DARA appears on serum protein electrophoresis (SPEP) and on serum immunofixation (sIFE) as an IgG kappa monoclonal immunoglobulin protein (M-protein), complicating the assessment of the patients’ response to therapy. A more ominous threat to patient safety can occur with the misinterpretation of the presence of a small t-mAb spike as being the residual product of the patient’s neoplastic clone, presented either as oligoclonality or new clonality, which could result in incorrect interpretation of failure to achieve remission. Methods: In this report, we describe a novel and cost-effective technique based on biotinylated recombinant CD38 and streptavidin-coated magnetic beads to capture and remove residual DARA present in PCM patient serum samples. The treated samples are then run like regular samples on SPEP and sIFE. We validated this simple technique in DARA-spiked PCM samples and patient samples on DARA treatment. Results: Our simple capture technique completely extracted DARA in all of the tested serum specimens and allowed the assessment of residual M-protein without DARA interference. The results were reproducible and highly specific for DARA, and did not have any impact on endogenous M-protein migration and quantification by SPEP and sIFE. The cost of this technique is much lower and it can be performed in-house with a very short turnaround time compared to the currently available alternative methods. There is a great need for such reflex technologies to avoid interpretation errors. Conclusions: This method is an effective way to eliminate DARA interference in SPEP and sIFE, and can be easily implemented in any clinical laboratory without any patent restriction. This simple technique can be adopted for other t-mAbs using their respective ligands and will help to reduce additional doses of toxic treatment and further testing in patients on t-mAbs with a false positive M-protein spike. MDPI 2020-04-14 /pmc/articles/PMC7235820/ /pubmed/32295157 http://dx.doi.org/10.3390/diagnostics10040219 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vakili, Hana
Koorse Germans, Sharon
Dong, Xiuhua
Kansagra, Ankit
Patel, Hetalkumari
Muthukumar, Alagarraju
Hashim, Ibrahim A.
Complete Depletion of Daratumumab Interference in Serum Samples from Plasma Cell Myeloma Patients Improves the Detection of Endogenous M-Proteins in a Preliminary Study
title Complete Depletion of Daratumumab Interference in Serum Samples from Plasma Cell Myeloma Patients Improves the Detection of Endogenous M-Proteins in a Preliminary Study
title_full Complete Depletion of Daratumumab Interference in Serum Samples from Plasma Cell Myeloma Patients Improves the Detection of Endogenous M-Proteins in a Preliminary Study
title_fullStr Complete Depletion of Daratumumab Interference in Serum Samples from Plasma Cell Myeloma Patients Improves the Detection of Endogenous M-Proteins in a Preliminary Study
title_full_unstemmed Complete Depletion of Daratumumab Interference in Serum Samples from Plasma Cell Myeloma Patients Improves the Detection of Endogenous M-Proteins in a Preliminary Study
title_short Complete Depletion of Daratumumab Interference in Serum Samples from Plasma Cell Myeloma Patients Improves the Detection of Endogenous M-Proteins in a Preliminary Study
title_sort complete depletion of daratumumab interference in serum samples from plasma cell myeloma patients improves the detection of endogenous m-proteins in a preliminary study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235820/
https://www.ncbi.nlm.nih.gov/pubmed/32295157
http://dx.doi.org/10.3390/diagnostics10040219
work_keys_str_mv AT vakilihana completedepletionofdaratumumabinterferenceinserumsamplesfromplasmacellmyelomapatientsimprovesthedetectionofendogenousmproteinsinapreliminarystudy
AT koorsegermanssharon completedepletionofdaratumumabinterferenceinserumsamplesfromplasmacellmyelomapatientsimprovesthedetectionofendogenousmproteinsinapreliminarystudy
AT dongxiuhua completedepletionofdaratumumabinterferenceinserumsamplesfromplasmacellmyelomapatientsimprovesthedetectionofendogenousmproteinsinapreliminarystudy
AT kansagraankit completedepletionofdaratumumabinterferenceinserumsamplesfromplasmacellmyelomapatientsimprovesthedetectionofendogenousmproteinsinapreliminarystudy
AT patelhetalkumari completedepletionofdaratumumabinterferenceinserumsamplesfromplasmacellmyelomapatientsimprovesthedetectionofendogenousmproteinsinapreliminarystudy
AT muthukumaralagarraju completedepletionofdaratumumabinterferenceinserumsamplesfromplasmacellmyelomapatientsimprovesthedetectionofendogenousmproteinsinapreliminarystudy
AT hashimibrahima completedepletionofdaratumumabinterferenceinserumsamplesfromplasmacellmyelomapatientsimprovesthedetectionofendogenousmproteinsinapreliminarystudy